Abstract

Although aging is associated with a higher risk of developing respiratory pathologies, very few studies have assessed the impact of age on the adverse effects of inhaled nanoparticles. Using conventional and transcriptomic approaches, this study aimed to compare in young (12–13-week-old) and elderly (19-month-old) fisher F344 rats the pulmonary toxicity of an inhaled nanostructured aerosol of titanium dioxide (TiO2). Animals were nose-only exposed to this aerosol at a concentration of 10 mg/m3 for 6 h per day, 5 days per week for 4 weeks. Tissues were collected immediately (D0), and 28 days after exposure (D28). A pulmonary influx of neutrophilic granulocytes was observed in exposed rats at D0, but diminished with time while remaining significant until D28. Similarly, an increased expression of several genes involved in inflammation at the two post-exposure time-points was seen. Apart from an age-specific pulmonary influx of lymphocyte, only slight differences in physio-pathological responses following TiO2 exposure between young and elderly animals were noticed. Conversely, marked age-related differences in gene expression profiles were observed making possible to establish lists of genes specific to each age group and post-exposure times. These results highlight different signaling pathways that were disrupted in rats according to their age.

Highlights

  • The rapid development of nanotechnology may lead to the exposure of workers to nanomaterials in many industrial sectors; the health effects of nanoparticles are still under investigation

  • In a previous work [12], we have showed that the nose-only inhalation exposure of young F344 rats to a TiO2 aerosol (10 mg/m3 ), 6 h a day, 5 days a week for 4 weeks, led to lung inflammation decreasing over time, and changed the modulation of gene expression profile after exposure

  • Results concerning the pulmonary effects of the inhaled aerosol in young rats were published previously by our laboratory [12]

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Summary

Introduction

The rapid development of nanotechnology may lead to the exposure of workers to nanomaterials in many industrial sectors; the health effects of nanoparticles are still under investigation. The main route of occupational exposure to such nanomaterials is inhalation since they can become aerosolized, especially during handling processes. The pulmonary toxicity of TiO2 nanoparticles has been extensively investigated, and despite the fact TiO2 has been classified as a poorly soluble low toxicity nanoparticle [4], inhalation studies with different rodent species and TiO2 samples with different physical and chemical characteristics have reported pulmonary inflammation [3,5]. Most studies on nanomaterial lung toxicity have used healthy young rodents, the general population includes groups of individuals more susceptible to toxicant exposure such as the elderly. Lung aging is characterized by a decline in lung function with a decrease

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